Amphetamine-sensitized animals show a sensorimotor gating and neurochemical abnormality similar to that of schizophrenia

被引:87
作者
Tenn, CC
Fletcher, PJ
Kapur, S
机构
[1] Ctr Addict & Mental Hlth, Clark Inst, Schizophrenia PET Ctr, Toronto, ON M5T 1R8, Canada
[2] Ctr Addict & Mental Hlth, Sect Biopsychol, Toronto, ON, Canada
[3] Univ Toronto, Dept Psychiat, Toronto, ON, Canada
基金
加拿大健康研究院;
关键词
amphetamine; schizophrenia; sensitization; dopamine; prepulse inhibition; raclopride;
D O I
10.1016/S0920-9964(03)00009-4
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
The aim of these studies was to examine whether amphetamine-induced sensitization in rats could be used as an animal model to study the basis of certain abnormalities seen in schizophrenia. Specifically, these experiments examined whether rats subjected to a sensitizing regimen of amphetamine would show the sensorimotor gating and greater amphetamine-induced displacement of radio-raclopride binding deficit that is observed in schizophrenia. In the first experiment, animals were divided into two groups with each rat receiving an intraperitoneal injection of amphetamine (AMPH) or saline (SAL) (I ml/kg) three times per week for 3 weeks for a total of nine injections. AMPH dose was increased weekly from I mg/kg in the first week to 3 mg/kg in the third. Twenty-two days after the last injection, prepulse inhibition (PPI) of the acoustic startle response was tested. In addition, rats were tested for the effects of a challenge dose of 0.5 mg/kg AMPH on locomotor activity and [H-3]raclopride (RAC) binding potential (BP) in the striatum. The tests for PPI confirmed that sensorimotor gating was disrupted in the AMPHinduced sensitized-state rats at baseline. The AMPH-sensitized rats also exhibited higher locomotor response to AMPH and a lower binding of striatal [H-3]raclopride when challenged with the drug. The results were replicated and even more pronounced in rats that were treated with AMPH for 5 weeks, with doses ranging from 1 mg/kg in the first week to 5 mg/kg in the fifth. These sensorimotor gating deficits and neurochemical (greater AMPH-induced displacement of radio-raclopride binding) abnormalities show similarities with the pathophysiology of schizophrenia and suggest that the AMPH-sensitized-state rats could be used to model certain aspects of schizophrenia. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:103 / 114
页数:12
相关论文
共 39 条
[1]  
Abi-Dargham A, 1998, AM J PSYCHIAT, V155, P761
[2]   Increased baseline occupancy of D2 receptors by dopamine in schizophrenia [J].
Abi-Dargham, A ;
Rodenhiser, J ;
Printz, D ;
Zea-Ponce, Y ;
Gil, R ;
Kegeles, LS ;
Weiss, R ;
Cooper, TB ;
Mann, JJ ;
Van Heertum, RL ;
Gorman, JM ;
Laruelle, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (14) :8104-8109
[3]   PRE-STIMULUS EFFECTS ON HUMAN STARTLE REFLEX IN NORMALS AND SCHIZOPHRENICS [J].
BRAFF, D ;
STONE, C ;
CALLAWAY, E ;
GEYER, M ;
GLICK, I ;
BALI, L .
PSYCHOPHYSIOLOGY, 1978, 15 (04) :339-343
[4]  
BRAFF DL, 1990, ARCH GEN PSYCHIAT, V47, P181
[5]  
BRAFF DL, 1992, ARCH GEN PSYCHIAT, V49, P206
[6]   Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia [J].
Braff, DL ;
Geyer, MA ;
Light, GA ;
Sprock, J ;
Perry, W ;
Cadenhead, KS ;
Swerdlow, NR .
SCHIZOPHRENIA RESEARCH, 2001, 49 (1-2) :171-178
[7]  
BRIER A, 1997, P NATL ACAD SCI USA, V94, P2569
[8]   Dissociative effects of apomorphine infusions into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine-induced locomotion [J].
Broersen, LM ;
Feldon, J ;
Weiner, I .
NEUROSCIENCE, 1999, 94 (01) :39-46
[9]   Behavioral changes and [123I]IBZM equilibrium SPECT measurement of amphetamine-induced dopamine release in rhesus monkeys exposed to subchronic amphetamine [J].
Castner, SA ;
Al-Tikriti, MS ;
Baldwin, RM ;
Seibyl, JP ;
Innis, RB ;
Goldman-Rakic, PS .
NEUROPSYCHOPHARMACOLOGY, 2000, 22 (01) :4-13
[10]  
DEUTCH AY, 1992, J NEURAL TRANSM-GEN, P61